BSCB Newsletter, Winter 2011

Jacques Monod Conference on cell division in time and space
11-15 September, 2010.  Roscoff, France.

This meeting covered a broad range of cell cycle research topics.  The talks were divided into ten sessions on asymmetric cell division, DNA replication and chromosome cohesion, modelling the cell cycle, late mitosis and cytokinesis, spindle assembly, spindle dynamics, organelles in mitosis, mitotic progression, nuclear dynamics and meiosis, and the spindle assembly checkpoint.

This conference in the peaceful seaside town of Roscoff was opened with the Plenary talk by Kim Nasmyth, University of Oxford. He described his laboratory's findings that the Rec8 kleisin subunit, as opposed to scc1, holds together the cohesin rings that maintain attachment of bivalent chromosomes during female meiosis from birth to ovulation. At the point of fertilisation the place of Rec8 is taken by the scc1 subunit, prior to the first mitosis.

Among the highlights were the two EMBO Young Investigator lectures. Monica Gotta, University of Geneva, Switzerland,  described a role for SPAT-1, the C.elegans homologue of Bora, in regulation of both cell polarity and cell cycle progression during asymmetric division. This is achieved in conjunction with Plk1 and Aurora A kinases. The second was from Philippe Pasero (Institut de Génétique Humaine, France), who has found that the known budding yeast replication stress-responsive kinases, Mec1 and Rad53, are also activated during a normal S phase at sites where transcription interferes with replication.

Sometimes multiple groups were approaching similar questions, for example how sister chromatid cohesion by the cohesin complex is regulated through S phase and into mitosis. During S phase the replication forks need to progress past the cohesin, while the sister chromatids must remain attached. Prasad Jallepalli (Memorial Sloan-Kettering Cancer Center, USA) showed that the RFC-Ctf18 complex regulates positioning and velocity of replication forks, and is required for acetylation of the smc3 subunit of cohesin. This acetylation is required for replication fork progression. In mammals, Sororin may then bind and stabilise cohesion rings post-replication. Work described by Jan-Michael Peters (Research Institute of Molecular Pathology, Austria), found that Sororin competes with the cohesin cofactor WAP1 for binding to the cohesin complex. His group found that loss of WAP1 in mice caused an excessive cohesion, while loss of Sororin caused the opposite effect. Sororin binds cohesin early in S phase, but this is reduced as cells enter prophase, when cohesion is lost along the chromosome arms in a WAP1-dependent manner. These findings were elaborated upon by Tomoko Nishiyama from the Peters laboratory in her poster, which described that Sororin association with cohesins is dependent upon cohesin acetylation following DNA replication, a mechanism which is conserved in Drosophila.

On the second day we moved on to mitosis. Tarun Kapoor (Rockefeller University, USA) described elegant in vitro experiments revealing that when a PRC1 homodimer interacts with a single microtubule it adopts a flexible conformation, while binding of both subunits to a pair of antiparallel microtubules forms a defined bridge. These bridges do not significantly slow the rate of microtubule sliding by kinesin 5, suggesting that PRC1 acts as an antiparallel microtubule tip tracker. Daniel Gerlich (Swiss Federal Institute of Tehnology Zurich, Switzerland) presented a purse-string model for abscission of cells during cytokinesis. In this model, spastin-mediated microtubule disassembly at the midbody facilitates contraction of the intercellular bridge by ESCRTIII complex-rich filaments that underlie the cell cortex.

In the talks on spindle assembly, Helder Maiato (Instituto de Biologia Molecular e Cellular, Portugal) spoke about the still controversial spindle matrix. He has found that the Drosophila nuclear-pore complex protein Megator and the spindle checkpoint protein Mad2 form a conserved complex that localises to a spindle matrix. Megator is proposed to act as a spatial regulator of the spindle assembly checkpoint here, by ensuring efficient loading of Mad2 onto unattached kinetochores.

The following day Sue Biggins (Fred Hutchinson Cancer Research Centre, USA) described the successful purification of functional kinetochores from yeast. These kinetochore particles were able to bind microtubules and remained attached to dynamic microtubule tips in a manner that was stabilised by tension. Furthermore the kinetochores decreased microtubule catastrophe events showing that microtubule tip dynamics are altered. Later Marina Bacac (University Hospital Lousanne CHUV, Switzerland) introduced a novel interphase role for mammalian securin and separase, during which they associate with cell membranes. Depletion of these proteins disrupts morphology and function of the Golgi Apparatus and endosomes.

One of the speakers on the last morning was Jon Pines (University of Cambridge) who described how the spindle assembly checkpoint regulates the choice of substrates degraded by the APC/C, by regulating the site on the APC/C to which the APC/C co-activator cdc20 binds.

This meeting was characterised throughout by a convivial atmosphere, lively scientific discussion and celebration of the fascinating cell cycle research being undertaken around the world.  The quality of the work being presented was excellent, and the enthusiasm of each delegate infectious. Particularly striking was the eagerness of everyone, even the most experienced principal investigators, to meet all the other attendees and hear about their work. I left the meeting inspired, and with useful feedback from my own poster. Even the traditional airport workers strike causing cancellation of my return flight was unable to dampen my enthusiasm! I am very grateful to the BSCB for contributing to the cost of my attendance at this meeting. I would encourage any other members who have the opportunity to attend this conference in future years to grasp it with both hands; it was the best meeting I have attended.

Fiona Hood,
Physiological Laboratory
University of Liverpool